Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis

Objective: Calprotectin is a major leucocyte protein, shown to correlate well with laboratory and clinical assessments in several inflammatory rheumatic diseases, and large concentrations of calprotectin have been found in synovial fluid from patients with rheumatoid arthritis (RA). The objective of the present study was to examine correlations between calprotectin and joint damage. Methods: 145 patients with RA were analysed cross sectionally with laboratory (calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), clinical (28 joint counts (tender, swollen), physician global VAS, DAS28 and RA Articular Damage score (RAAD)), and radiographic (plain hand radiographs; modified Sharp’s method) measurements, on the same day. Results: Calprotectin showed a highly significant correlation with measures of joint damage; modified Sharp score r = 0.43 (p<0.001) and RAAD r = 0.40 (p<0.001). The association with modified Sharp score and RAAD score was maintained after adjustment for CRP, ESR, rheumatoid factor, DAS28, sex, and age in a multiple regression analysis (p = 0.018 and p = 0.04, respectively), while neither CRP nor ESR showed any independent associations. Highly significant correlations (p<0.001) were also found between calprotectin and both laboratory and clinical markers of inflammation. Conclusion: Calprotectin was found to significantly and independently explain the variation in the radiological and clinical assessments of joint damage. Longitudinal studies are required to examine whether calprotectin may predict the progression of joint damage in RA.

[1]  I. Dale,et al.  Release and Quantitation of a Leucocyte Derived Protein (L1) , 2009 .

[2]  D. M. van der Heijde,et al.  Association of early radiographic damage with impaired physical function in rheumatoid arthritis: a ten-year, longitudinal observational study in 238 patients. , 2006, Arthritis and rheumatism.

[3]  T. Lyberg,et al.  Increase in plasma calprotectin during long‐distance running , 2005, Scandinavian journal of clinical and laboratory investigation.

[4]  I. Thorey,et al.  MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. , 2004, Blood.

[5]  D. Foell,et al.  Proinflammatory S100 proteins in arthritis and autoimmune disease. , 2004, Arthritis and rheumatism.

[6]  K. Clauser,et al.  Use of mass spectrometry to identify protein biomarkers of disease severity in the synovial fluid and serum of patients with rheumatoid arthritis. , 2004, Arthritis and rheumatism.

[7]  P. Tessier,et al.  Monosodium urate monohydrate crystals induce the release of the proinflammatory protein S100A8/A9 from neutrophils , 2004, Journal of leukocyte biology.

[8]  M. Frosch,et al.  Myeloid related proteins MRP8/MRP14 may predict disease flares in juvenile idiopathic arthritis. , 2004, Clinical and experimental rheumatology.

[9]  D. Foell,et al.  Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arthritis. , 2003, Arthritis and rheumatism.

[10]  B. Dijkmans,et al.  The predictive value of anti-cyclic citrullinated peptide antibodies in early arthritis. , 2003, The Journal of rheumatology.

[11]  S. McColl,et al.  Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis. , 2003, Arthritis and rheumatism.

[12]  B. Bresnihan,et al.  Increased perivascular synovial membrane expression of myeloid-related proteins in psoriatic arthritis. , 2003, Arthritis and rheumatism.

[13]  M. Frosch,et al.  Myeloid related protein 8 and 14 secretion reflects phagocyte activation and correlates with disease activity in juvenile idiopathic arthritis treated with autologous stem cell transplantation , 2003, Annals of the rheumatic diseases.

[14]  T. Uchida,et al.  Application of a novel protein biochip technology for detection and identification of rheumatoid arthritis biomarkers in synovial fluid. , 2002, Journal of proteome research.

[15]  R. Jonsson,et al.  Leukocyte protein calprotectin and outcome in rheumatoid arthritis , 2002, Scandinavian journal of rheumatology.

[16]  H. B. Bernelot Moens,et al.  The rheumatoid arthritis articular damage score: first steps in developing a clinical index of long term damage in RA , 2002, Annals of the rheumatic diseases.

[17]  B. Dijkmans,et al.  Predictors of radiographic joint damage in patients with early rheumatoid arthritis , 2001, Annals of the rheumatic diseases.

[18]  M. V. van Leeuwen,et al.  The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. , 2000, Arthritis and rheumatism.

[19]  N. Wulffraat,et al.  Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis. , 2000, Arthritis and rheumatism.

[20]  M. Frosch,et al.  Expression of myeloid related proteins (MRP) 8 and 14 and the MRP8/14 heterodimer in rheumatoid arthritis synovial membrane. , 1999, The Journal of rheumatology.

[21]  P. Shekelle,et al.  How to read radiographs according to the Sharp/van der Heijde method. , 1999 .

[22]  C. Kerkhoff,et al.  Novel insights into structure and function of MRP8 (S100A8) and MRP14 (S100A9). , 1998, Biochimica et biophysica acta.

[23]  O. Børmer,et al.  Fecal calprotectin concentration in patients with colorectal carcinoma , 1998, Diseases of the colon and rectum.

[24]  T. Lyberg,et al.  Functional and clinical aspects of the myelomonocyte protein calprotectin. , 1997, Molecular pathology : MP.

[25]  F. Guillemin,et al.  Correlates of functional disability in early rheumatoid arthritis: a cross-sectional study of 706 patients in four European countries. , 1996, British journal of rheumatology.

[26]  P. Vaglum,et al.  The relationship between self-reported pain and sociodemographic variables, anxiety, and depressive symptoms in rheumatoid arthritis. , 1995, The Journal of rheumatology.

[27]  T. Kvien,et al.  A longitudinal study of calprotectin as an inflammatory marker in patients with reactive arthritis. , 1995, Clinical and experimental rheumatology.

[28]  M. V. van Leeuwen,et al.  IgM, IgA, and IgG rheumatoid factors in early rheumatoid arthritis predictive of radiological progression? , 1995, Scandinavian journal of rheumatology.

[29]  R. Jonsson,et al.  Measurement of plasma calprotectin as an indicator of arthritis and disease activity in patients with inflammatory rheumatic diseases. , 1994, The Journal of rheumatology.

[30]  G. Hughes,et al.  Calprotectin in Patients with Systemic Lupus Erythematosus: Relation to Clinical and Laboratory Parameters of Disease Activity , 1993, Lupus.

[31]  A. Røseth,et al.  Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. , 1992, Scandinavian journal of gastroenterology.

[32]  A. Zwinderman,et al.  Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study. , 1992, Annals of the rheumatic diseases.

[33]  J. Brun,et al.  Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity. , 1992, The Journal of rheumatology.

[34]  N. Hogg,et al.  Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. , 1991, The Journal of biological chemistry.

[35]  M. Fagerhol,et al.  The leukocyte protein L1 in plasma and synovial fluid from patients with rheumatoid arthritis and osteoarthritis. , 1991, Scandinavian journal of rheumatology.

[36]  P. Mowinckel,et al.  The L1 protein as a new indicator of inflammatory activity in patients with juvenile rheumatoid arthritis. , 1991, The Journal of rheumatology.

[37]  F. Arnett.  Revised criteria for the classification of rheumatoid arthritis. , 1990, Orthopedic nursing.

[38]  M. Fagerhol,et al.  A longitudinal study of the leukocyte protein L1 as an indicator of disease activity in patients with rheumatoid arthritis. , 1989, The Journal of rheumatology.

[39]  D. Heijde,et al.  EFFECTS OF HYDROXYCHLOROQUINE AND SULPHASALAZINE ON PROGRESSION OF JOINT DAMAGE IN RHEUMATOID ARTHRITIS , 1989, The Lancet.

[40]  C. Hayward,et al.  Expression pattern of two related cystic fibrosis-associated calcium-binding proteins in normal and abnormal tissues. , 1988, Journal of cell science.

[41]  E. Jellum,et al.  The Leucocyte L1 Protein: Identity with the Cystic Fibrosis Antigen and the Calcium‐Binding MRP‐8 and MRP‐14 Macrophage Components , 1988, Scandinavian journal of immunology.

[42]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[43]  M. Fagerhol,et al.  The major leukocyte protein L1 as an indicator of inflammatory joint disease. , 1988, Scandinavian journal of rheumatology. Supplement.

[44]  R. G. Clerc,et al.  Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis , 1987, Nature.

[45]  Veronica van Heyningen,et al.  A clue to the basic defect in cystic fibrosis from cloning the CF antigen gene , 1987, Nature.

[46]  P. Brandtzaeg,et al.  Distribution of a new myelomonocytic antigen (L1) in human peripheral blood leukocytes. Immunofluorescence and immunoperoxidase staining features in comparison with lysozyme and lactoferrin. , 1985, American journal of clinical pathology.

[47]  I. Dale,et al.  Purification and partial characterization of a highly immunogenic human leukocyte protein, the L1 antigen. , 1983, European journal of biochemistry.

[48]  I. Dale,et al.  A radioimmunoassay for a granulocyte protein as a marker in studies on the turnover of such cells. , 1980, Bulletin europeen de physiopathologie respiratoire.

[49]  Erik Carlsson,et al.  A methodologic study , 1977 .